Long-term tamoxifen use increases risk of an aggressive, hard to treat type of second breast cancer

Study Finds a More Than Four-Fold Increased Risk of ER Negative
Second Cancers

SEATTLE, Aug. 25, 2009 – While long-term tamoxifen
use among breast cancer survivors decreases their risk of
developing the most common, less aggressive type of second breast
cancer, such use is associated with a more than four-fold increased
risk of a more aggressive, difficult-to-treat type of cancer in the
breast opposite, or contralateral, to the initial tumor. These
findings by Christopher Li, M.D., Ph.D., and colleagues at Fred
Hutchinson Cancer Research Center were published online Aug. 25 in
the journal Cancer Research.

Hormonal therapy with drugs like tamoxifen is one of the most
common treatments for breast cancer because it has been shown to
reduce the risk of dying from the disease but, as this study
suggests, it does have risks.

Comparing breast-cancer patients who received the
estrogen-blocking drug tamoxifen to those who did not, the
researchers found that while the drug was associated with a 60
percent reduction in estrogen receptor-positive, or ER positive,
second breast cancer – the more common type, which is
responsive to estrogen-blocking therapy – it also appeared to
increase the risk of ER negative second cancer by 440 percent.
"This is of concern, given the poorer prognosis of ER-negative
tumors, which are also more difficult to treat," said Li, an
associate member of the Hutchinson Center's Public Health Sciences
Division.

These findings confirm preliminary research by Li and
colleagues, published in 2001, which was the first to suggest a
link between long-term tamoxifen use and an increased risk of
ER-negative second cancers. "The earlier study had a number of
limitations. For example, we did not have information on the
duration of tamoxifen therapy the women received," Li said. "The
current study is larger, is based on much more detailed data, and
is the first study specifically designed to determine whether
tamoxifen use among breast cancer survivors influences their risk
of different types of second breast cancers," Li said.

This new study assessed history of tamoxifen use among 1,103
breast cancer survivors from the Seattle-Puget Sound region who
were initially diagnosed with ER positive breast cancer between the
ages of 40 and 79. Of these, 369 of the women went on to develop a
second breast cancer. Nearly all of the women in the study who took
adjuvant hormonal therapy used tamoxifen specifically. Detailed
information about tamoxifen use was ascertained from telephone
interviews and medical record reviews.

While the study confirmed a strong association between long-term
tamoxifen therapy and an increased risk of ER-negative second
cancer, it does not suggest that breast cancer survivors should
stop taking hormone therapy to prevent a second cancer, Li
said.

"It is clear that estrogen-blocking drugs like tamoxifen have
important clinical benefits and have led to major improvements in
breast cancer survival rates. However, these therapies have risks,
and an increased risk of ER negative second cancer may be one of
them. Still, the benefits of this therapy are well established and
doctors should continue to recommend hormonal therapy for breast
cancer patients who can benefit from it," Li said.

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The National Cancer Institute funded the research.

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